Self-emulsifying cannabidiol formulations

ABSTRACT

The present invention is directed to a self-emulsifying cannabidiol composition containing one or more surfactants. The present invention is further directed to a method of treating a disease comprising administering a composition of the present invention to a subject in need thereof. The present invention is further directed to a method of treating withdrawal symptoms.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. application No. 62/847,991,filed May 15, 2019. The entire contents are which are herebyincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The present invention is directed to a self-emulsifying cannabidiolcomposition containing one or more surfactants. The present invention isfurther directed to a method of treating a disease comprisingadministering a composition of the present invention to a subject inneed thereof. The present invention is further directed to a method oftreating withdrawal symptoms comprising administering a composition ofthe present invention to a subject in need thereof.

BACKGROUND OF THE INVENTION

Cannabidiol, (−)-trans-2-p-mentha-1,8-dien-3-yl-5-pentylresorcinol, isnon-psychoactive and has shown promise in treating numerous diseases anddisorders. Cannabidiol has been approved by the United States Food andDrug Administration for to treat Lennox-Gastaut syndrome, Dravetsyndrome. Further, cannabidiol, may be suitable for the treatment ofdiseases or disorders, or symptoms of diseases or disorders, such asmycolonic seizures, juvenile mycolonic epilepsy, refractory epilepsy,schizophrenia, juvenile spasms, West syndrome, refractory infantilespasms, infantile spasms, tubular sclerosis complex, brain tumors,neuropathic pain, cannabis use disorder, post-traumatic stress disorder,anxiety, early psychosis, Alzheimer's Disease autism, and withdrawalfrom opioids, cocaine, heroin, amphetamines, and nicotine.

While there are many dosage forms of cannabidiol the most popular formis oral. Oral formulations of cannabidiol are more convenient and aremore likely to lead to patient compliance. Oral dosages of cannabidiolhas been formulated in hydroalcoholic and lipid-based formulations. Theissue with these oral formulations is that they have poor solubility andthus poor bioavailability in water such as encountered in thegastrointestinal tract when imbibed.

To combat poor solubility formulation scientist have developedSelf-Emulsifying Drug Delivery system (SEDDS). SEDDS have shown toimprove solubilization of poorly soluble drugs, improve thebioavailability due to reduced first pass metabolism and improvedabsorption through lymphatic transport by forming chylomicrons. However,developing a SEDDS is a painstaking task that differs for each activeingredient. The specific excipients and concentrations may only bediscovered through intense formulation research.

Accordingly, there is a need in the art for a cannabidiol formulationthat self emulsifies in contact with an aqueous medium.

SUMMARY OF THE INVENTION

The present invention is directed to a self-emulsifying cannabidiolcomposition comprising from about 1 to about 40% w/w cannabidiol andfrom about 40% to about 99% w/w of one or more surfactants selected frompolyethylene glycol 40 hydrogenated castor oil, caprylocaproylpolyoxyl-8 glycerides, lauoryl polyoxylglycerides, oleoyl polyoxyl-6glycerides, linoleoyl polyoxyl-6 glycerides, lauroyl polyoxyl-6glycerides, propylene glycol monocaprylate, propylene glycolmonolaurate, polyglyceryl-3 dioleate, a polysorbate and sorbitanmonooeate.

The present invention is further directed to a self-emulsifyingcannabidiol composition comprising:

-   -   from about 5% to about 35% w/w cannabidiol;    -   from about 2% to about 60% w/w polyethylene glycol 40        hydrogenated castor oil;    -   from about 2% to about 50% w/w of a surfactant selected from        caprylocaproyl polyoxyl-8 glycerides, linoleoyl polyoxyl-6        glyceride or a combination thereof; and    -   from about 0.1% to about 2% w/w alpha tocopherol.

The present invention is further directed to a method of treating adisease selected from Prader-Willi syndrome, obesity, graft versus hostdisease, gelastic seizures/hypothalamic hamartoma, neonatal seizures,dystonia, central pain syndromes, phantom limb pain, multiple sclerosis,traumatic brain injury, radiation therapy, acute graft versus hostdisease, chronic graft versus host disease, T-cell autoimmune disorders,colitis, Dravet Syndrome, Lennox Gastaut Syndrome, mycolonic seizures,juvenile mycolonic epilepsy, refractory epilepsy, childhood absenceepilepsy, schizophrenia, juvenile spasms, West syndrome, infantilespasms, refractory infantile spasms, tuberous sclerosis complex, braintumors, neuropathic pain, cannabis use disorder, post-traumatic stressdisorder, anxiety, early psychosis, Alzheimer's Disease, autism, acne,Parkinson's disease, social anxiety disorder, depression, diabeticretinopathy, diabetic nephropathy, diabetic neuropathy, ischemic injuryof heart, ischemic injury of brain, chronic pain syndrome, andrheumatoid arthritis comprising administering a composition of thepresent invention to a subject in need thereof.

The present invention is further directed to a method of treatingwithdrawal symptoms comprising administering a composition of thepresent invention to a subject in need thereof, wherein the withdrawalsymptoms are caused by the subject reducing or quitting use of anopioid, cocaine, heroin, an amphetamine or nicotine.

BRIEF DESCRIPTION OF THE DRAWINGS

The subject matter of the present disclosure is particularly pointed outand distinctly claimed in the concluding portion of the specification. Amore complete understanding of the present disclosure, however, may bestbe obtained by referring to the detailed description and claims whenconsidered in connection with the drawing figures.

FIG. 1 . Shows an illustration of plasma concentration of cannabidiolafter administration of Composition 5 from time 0 to 96 hours.

FIG. 2 . Shows an illustration of plasma concentration of cannabidiolafter administration of Composition 5 from time 0 to 8 hours.

DETAILED DESCRIPTION OF THE INVENTION

The detailed description of exemplary embodiments herein makes referenceto the accompanying drawings which show exemplary embodiments by way ofillustration and their best mode. While these exemplary embodiments aredescribed in sufficient detail to enable those skilled in the art topractice the inventions, it should be understood that other embodimentsmay be realized and that logical, chemical, and mechanical changes maybe made without departing from the spirit and scope of the inventions.Thus, the detailed description herein is presented for purposes ofillustration only and not of limitation. For example, the steps hereinrecited in any of the method of process descriptions may be executed inany order and are not necessarily limited to the order presented.Furthermore, any reference to singular includes plural embodiments, andany reference to more than one component or step may include a singularembodiment or step. Also, any reference to attached, fixed, connected orthe like may include permanent, removable, temporary, partial, fulland/or any other possible attachment option. Additionally, any referenceto without contact (or similar phrases) may also include reduced contactor minimal contact.

Applicant unexpectedly found that the presence of particular surfactantsin a cannabidiol composition form an emulsion with an average globulesize capable of passing through the gastrointestinal tract whendispersed in an aqueous medium.

In one embodiment, the present invention is directed to aself-emulsifying cannabidiol composition comprising from about 1 toabout 40% w/w cannabidiol and from about 40% to about 99% w/w of one ormore surfactants selected from polyethylene glycol (“PEG”) 40hydrogenated castor oil, caprylocaproyl polyoxyl-8 glycerides, lauorylpolyoxylglycerides, oleoyl polyoxyl-6 glycerides, linoleoyl polyoxyl-6glycerides, lauroyl polyoxyl-6 glycerides, propylene glycolmonocaprylate, propylene glycol monolaurate, polyglyceryl-3 dioleate, apolysorbate and sorbitan monooleate.

In a preferred embodiment, the present invention is further directed toa self-emulsifying cannabidiol composition comprising:

-   -   from about 5% to about 35% w/w cannabidiol;    -   from about 2% to about 60% w/w PEG 40 hydrogenated castor oil;    -   from about 2% to about 50% w/w of a surfactant selected from        caprylocaproyl polyoxyl-8 glycerides, linoleoyl polyoxyl-6        glyceride or a combination thereof; and    -   from about 0.1% to about 2% w/w alpha tocopherol.

Cannabidiol may be present in compositions of the present invention at aconcentration from about 0.1% to about 50% w/w, preferably from about 1%to about 40% w/w, more preferably from about 5% to about 35% w/w, evenmore preferably from about 10% to about 30% w/w or about 10% to about20% w/w.

Surfactants suitable for use in the present invention include, but arenot limited to, PEG 40 hydrogenated castor oil, caprylocaproylpolyoxyl-8 glycerides, lauoryl polyoxylglycerides, oleoyl polyoxyl-6glycerides, linoleoyl polyoxyl-6 glycerides, lauroyl polyoxyl-6glycerides, propylene glycol monocaprylate, propylene glycolmonolaurate, polyglyceryl-3 dioleate, a polysorbate and sorbitanmonooleate. In a preferred embodiment, surfactants may be selected fromPEG 40 hydrogenated castor oil, caprylocaproyl polyoxyl-8 glycerides,linoleoyl polyoxyl-6 glycerides, polyglyceryl-3 dioleate, polysorbate 80or a combination thereof.

The one or more surfactants may be present in compositions of thepresent invention at a concentration from about 1% to about 99% w/w,preferably from about 40% to about 99% or from about 2% to about 50%w/w, even more preferably from about 40% to about 80% w/w or from about20% to about 40% w/w and yet even more preferably from about 44% toabout 78% w/w.

Polyethylene glycol (“PEG”) 40 hydrogenated castor oil may be present incompositions of the present invention at a concentration from about 2%to about 60% w/w, preferably from about 10% to about 50% w/w and morepreferably from about 10% to about 40% w/w.

Polyglyceryl-3 dioleate may be present in compositions of the presentinvention at a concentration from about 1% to about 15% w/w, preferablyfrom about 2% to about 12% w/w.

Caprylocaproyl polyoxyl-8 glycerides may be present in compositions ofthe present invention at a concentration from about 1% to about 30% w/w,more preferably from about 3% to about 26% w/w.

Linoleoyl polyoxyl-6 glycerides may be present in compositions of thepresent invention at a concentration from about 1% to about 30% w/w,more preferably from about 4% to about 23% w/w.

Polysorbate 80 may be present in compositions of the present inventionat a concentration from about 1% to about 10% w/w, more preferably fromabout 2% to about 6% w/w.

Oils suitable for use in compositions of the present invention include,but are not limited to, glyceryl monolinoleate, glyceryl monooleate,propylene glycol dicaprylocaprate, glycerol monostearate 40-55, a mediumchain triglyceride or a combination thereof. In a preferred embodiment,the oil is a medium chain triglyceride, preferably a C8/C10 medium chaintriglyceride.

The one or more oils may be present in compositions of the presentinvention at a concentration from about 1% to about 50% w/w, preferablyfrom about 5% to about 30% w/w, more preferably from about 5% to about25% w/w.

Medium chain triglycerides may be present in compositions of the presentinvention at a concentration from about 1% to about 30% w/w, preferablyfrom about 9% to about 24% w/w.

Cosolvents suitable for use in the present invention include, but arenot limited to, propylene glycol, polyethylene glycol, ethanol or acombination thereof.

The one or more cosolvents may be present in compositions of the presentinvention at a concentration from about 1% to about 50% w/w, preferablyfrom about 5% to about 30% w/w, even more preferably from about 12% toabout 21% w/w.

Ethanol may be present in compositions of the present invention at aconcentration from about 1% to about 20% w/w, preferably from about 5%to about 15% w/w, even more preferably from about 10% to about 15% w/wand most preferably from about 12% to about 14% w/w.

Propylene glycol may be present in compositions of the present inventionat a concentration from about 1% to about 20% w/w, preferably from about5% to about 15% w/w, even more preferably from about 5% to about 10% w/wand most preferably from about 8% to about 10% w/w.

Antioxidants suitable for use in the present invention include, but arenot limited to, alpha tocopherol, butylated hydroxy anisole, butylatedhydroxy toluene, ascorbyl palmitate, ascorbic acid, sodium ascorbate,sodium metabisulfite, EDTA, citric acid, sodium bisulfite, sodiumthiosulfate, thioglycerol, propyl gallate or a combination thereof. In apreferred embodiment, the antioxidant is alpha tocopherol, ascorbylpalmitate or a combination thereof.

The one or more antioxidants may be present in compositions of thepresent invention at a concentration from about 0.01% to about 2% w/w,preferably from about 0.05% to about 1% w/w and even more preferablyfrom about 0.1% to about 0.5% w/w.

Alpha tocopherol may be present in compositions of the present inventionat a concentration from about 0.01% to about 2% w/w, preferably fromabout 0.01% to about 1% w/w, even more preferably from about 0.05% toabout 0.5% w/w and yet more preferably from about 0.05% to about 0.4%w/w.

Ascorbyl palmitate may be present in compositions of the presentinvention at a concentration from about 0.01% to about 2% w/w,preferably from about 0.01% to about 1% w/w and even more preferablyfrom about 0.05% to about 0.2% w/w.

In another embodiment, the composition of the present invention does notcontain sesame oil, castor oil, olive oil or water.

In a preferred embodiment, the compositions of the present inventionform an emulsion having an average globule size from about 20 to about5,000 nanometers when dispersed in an aqueous medium, preferably fromabout 30 to about 600 nanometers, even more preferably from about 100 toabout 1,000 nanometers and yet more preferably from about 100 to about300 nanometers. In a more preferred embodiment, the aqueous medium isgastric fluid.

In another preferred embodiment, the compositions of the presentinvention emulsifies in less than 30 minutes upon contact with anaqueous medium including gastric fluid.

In another preferred embodiment, the compositions of the presentinvention are contained in a soft or a hard gelatin capsule.

In a most preferred embodiment, the present invention is directed to aself-emulsifying cannabidiol composition comprising:

-   -   about 20.5% w/w cannabidiol;    -   about 12.0% w/w ethanol;    -   about 9.0% w/w propylene glycol;    -   about 17.0/w/w polyethylene glycol 40 hydrogenated castor oil;    -   about 26.0% w/w caprylocaproyl polyoxyl-8 glycerides;    -   about 4.0% w/w linoleoyl polyoxyl-6 glycerides; and    -   about 0.4% w/w alpha tocopherol,        wherein the composition forms an emulsion having an average        globule size of about 201 nanometers when dispersed in an        aqueous medium.

In another embodiment, the present invention is directed to a method oftreating a disease selected from Prader-Willi syndrome, obesity, graftversus host disease, gelastic seizures/hypothalamic hamartoma, neonatalseizures, dystonia, central pain syndromes, phantom limb pain, multiplesclerosis, traumatic brain injury, radiation therapy, acute graft versushost disease, chronic graft versus host disease, T-cell autoimmunedisorders, colitis, Dravet Syndrome, Lennox Gastaut Syndrome, mycolonicseizures, juvenile mycolonic epilepsy, refractory epilepsy, childhoodabsence epilepsy, schizophrenia, juvenile spasms, West syndrome,infantile spasms, refractory infantile spasms, tuberous sclerosiscomplex, brain tumors, neuropathic pain, cannabis use disorder,post-traumatic stress disorder, anxiety, early psychosis, Alzheimer'sDisease, autism, acne, Parkinson's disease, social anxiety disorder,depression, diabetic retinopathy, diabetic nephropathy, diabeticneuropathy, ischemic injury of heart, ischemic injury of brain, chronicpain syndrome, and rheumatoid arthritis comprising administering acomposition of the present invention to a subject in need thereof.

In another embodiment, the present invention is directed to a method oftreating withdrawal symptoms comprising administering a composition ofthe present invention to a subject in need thereof, wherein thewithdrawal symptoms are caused by the subject reducing or quitting useof an opioid, cocaine, heroin, an amphetamine or nicotine.

As used herein, all numerical values relating to amounts, weights, andthe like, that are defined as “about” each particular value is plus orminus 10%. For example, the phrase “about 10% w/w” is to be understoodas “9% w/w to 11% w/w.” Therefore, amounts within 10% of the claimedvalue are encompassed by the scope of the claims.

As used herein “% w/w” and “percent w/w” refer to the percent weight ofthe total formulation.

The disclosed embodiments are simply exemplary embodiments of theinventive concepts disclosed herein and should not be considered aslimiting, unless the claims expressly state otherwise.

The following examples are intended to illustrate the present inventionand to teach one of ordinary skill in the art how to use theformulations of the invention. They are not intended to be limiting inany way.

EXAMPLES Example 1—Preparation of Compositions of the Invention

TABLE 1 Compositions of the Invention % w/w 1 2 3 4 5 Cannabidiol 20.530.5 20.4 10.2 10.0 Ethanol 12.0 12.0 12.0 12.0 12.0 Propylene Glycol9.0 8.0 10.0 10.0 — PEG 40 hydrogenated castor oil 17.1 13.0 17.2 13.040.0 Polyglyceryl-3 dioleate 4.7 5.2 2.3 2.3 12.0 Caprylocaproylpolyoxyl-8 glycerides 26.0 19.5 25.5 26.0  3.0 Linoleoyl polyoxyl-6glycerides 4.3 6.5 — — 23.0 C8/C10 medium chain triglycerides — — 9.523.4 — Alpha-tocopherol (Vitamin E) 0.4 0.3 0.3 0.3 — Polysorbate 80 6.05.0 2.8 2.8 —

Cremophor® RH40 was used as the source for polyethylene glycol 40hydrogenated castor oil and is a registered trademark of and availablefrom BASF SE corporation.

Plurol® Oleique CC 497 was used as the source of polyglyceryl-3 dioleateand is a registered trademark of and available from Gattefosse SAS.

Labrasol® was used as the source of caprylocaproyl polyoxyl-8 glyceridesand is a registered trademark of and available from Gattefosse SAS.

Labrafil® M 2125 CS was used as the source of linoleoyl polyoxyl-6glycerides and is a registered trademark of and available fromGattefosse SAS.

Miglyol® 812 was used as the source of C8/C10 medium chain triglyceridesand is a registered trademark of and available from Cremer Oleo GMBH &Co.

Method

Alpha-tocopherol and cannabidiol were dissolved in ethanol to create amixture while mixing. Propylene glycol was then added to this mixturefollowed by rest of the excipients and mixed well. Polyethylene glycol(“PEG”) 40 hydrogenated castor oil was melted before being added to themixture. Emulsification time and globule size was measured.Emulsification time is the time it takes 1 gram of the composition tocompletely disperse in about 200 milliliters of 0.1 N HCl solution whilestirring. Globule size is measured using Nicomp ZLS Z3000.

TABLE 2 Emulsification time and globule size Emulsification Time GlobuleSize (min) (nm) Composition 1 <1 201.1 ± 112.65 Composition 2 <1 563.7 ±525.95 Composition 3 <1 291.9 ± 196.36 Composition 4 <1 216.1 ± 66.32 Composition 5 12 34.5 ± 9.8 Results

Compositions 1-4 emulsified in less than 1 minute. Composition 5 took 12minutes to emulsify. Compositions 1, 3 and 4 created an emulsion havingan average globule size of from 201.1 to 291.9 nanometers uponemulsification. Composition 2 created an emulsion having an averageglobule size of 563.7 nanometers upon emulsification. Composition 5created an emulsion having an average globule size of 34.5 nanometers.

Example 2—Stability of Composition 6

TABLE 3 Composition 6 % w/w 6 Cannabidiol 18.18 Ethanol 14.0 PEG 40hydrogenated castor oil 34.67 Polyglyceryl-3 dioleate 9.0 Caprylocaproylpolyoxyl-8 glycerides 3.0 Linoleoyl polyoxyl-6 glycerides 21.0Alpha-tocopherol (Vitamin E) 0.05 Ascorbyl palmitate 0.1Method

Composition 6 from Table 3, above, was prepared as in Example 1, above,and subjected to 40° C.±2° C. and 75±5% relative humidity (“RH”) for 2months and 25° C.±2° C. and 60±5% RH for 3 months. Results can be seenin Tables 4 and 5, below.

TABLE 4 Stability of Composition 6 at 40° C. ± 2° C. and 75 ± 5% RH RRTT = 0 1 Month 2 Month Physical appearance Clear, Clear, Clear, yellowyellow yellow colored colored colored Assay (% of Initial 100.00    96.37    94.24    Conc.) Delta 9-tetra- 1.761 0.01% 0.01% 0.01%hydrocannabinol Trans-(1R,6R)-3′- 1.865 0.04% 0.03% 0.03%methyl-cannabidiol Unknown Impurity 0.319 ND 0.01% 0.02% 0.373 ND ND0.01% 0.390 ND ND 0.01% 0.436 ND ND 0.02% 0.459 ND 0.02% 0.05% 0.479 ND0.02% 0.06% 0.500 0.01% 0.05% 0.16% 0.592 ND 0.01% ND 0.681 ND ND 0.01%0.771 0.05% 0.05% 0.05% 0.789 ND 0.02% 0.06% 0.819 0.02% 0.02% 0.01%0.825 ND ND 0.01% 0.848 ND ND 0.01% 2.075 ND 0.01% ND Total Impurities0.08% 0.21% 0.48% RRT denotes relative retention time

TABLE 5 Stability of Composition 6 at 25° C. ± 2° C. and 60 ± 5% RH RRTT = 0 1 Month 2 Month 3 Month Physical appearance Clear, Pale Clear,Pale Clear, Pale Clear, Pale yellow yellow yellow yellow Assay (% ofInitial Conc.) 100.00     98.58    96.90    96.31    Delta9-tetra-hydrocannabinol 1.761 0.01% 0.01% 0.01% 0.01%Trans-(1R,6R)-3′-methyl- 1.865 0.04% 0.03% 0.03% 0.03% cannabidiolCis-cannabidiol 1.453 0.01% 0.01% 0.01% 0.01% Unknown Impurity 0.313 NDND 0.01% 0.01% 0.374 ND ND ND 0.02% 0.396 ND 0.01% ND ND 0.452 ND ND ND0.01% 0.481 ND ND ND 0.01% 0.500 0.01% 0.01% 0.01% 0.01% 0.771 0.05%0.05% 0.05% 0.06% 0.819 0.02% 0.02% 0.02% 0.02% 2.075 ND 0.01% ND NDTotal Impurities 0.08% 0.10% 0.09% 0.14% ND denotes not detected

As seen in Tables 4 and 5, Composition 6 had only 0.48% total impuritiesafter 2 months at 40° C. and 0.14% total impurities after 3 months at25° C. Thus, compositions of the present invention are stable.

Example 3. Pharmacokinetic Study in Dogs

Method

In-vivo bioavailability and pharmacokinetics of Composition 5 wasevaluated in Beagle dogs. Specifically, five male Beagle dogs weighingfrom about 5 to about 11 kilograms were fasted overnight before dosing.Each Beagle dog was then administered 200 milligrams of cannabidiol inthe form of Composition 5. Blood samples were collected at 0, 15 and 30minutes and 1, 2, 3, 4, 8, 12, 24, 48, 72 and 96 hours after dosing.

The following pharmacokinetic parameters were calculated: peakconcentration in plasma (“C_(max)”), time to peak concentration(“T_(max)”) and area under the concentration-time curve (“AUC”). Resultsof this study can be seen in Table 6, below and in FIGS. 1 and 2 .

TABLE 6 Pharmacokinetic parameters Cmax (ng/mL) 672.84 ± 400.68 Tmax (h)3 AUC (ng/mL*h)  0-1 h 175.0 ± 76.8   0-4 h  1881 ± 952.7 0-12 h 3448.9± 1936.3 0-24 h 3971.0 ± 2250.9 0-48 h 4446.5 ± 2488.8 0-96 h 4910.8 ±2750.1Results

As seen in Table 6, Composition 5 provided a C_(max) of 672.84 nanogramsper milliliter (“ng/mL”) and a T_(max) of 3 hours. Further, Composition6 provided an AUC of 175.0 at 1 hour, 1,881 at 4 hours, 3448.9 at 12hours, 3971.0 at 24 hours, 4446.5 at 48 hours and 4910.8 at 96 hours.

Benefits, other advantages, and solutions to problems have beendescribed herein with regard to specific embodiments. Furthermore, theconnecting lines shown in various figures contained herein are intendedto represent exemplary functional relationships and/or physicalcouplings between the various elements. It should be noted that manyalternative or additional functional relationships or physicalconnections may be present in a practical system. However, the benefits,advantages, solutions to problems, and any elements that may cause anybenefit, advantage, or solution to occur or become more pronounced arenot to be construed as critical, required, or essential features orelements of the inventions. The scope of the inventions is accordinglyto be limited by nothing other than the appended claims, in whichreference to an element in the singular is not intended to mean “one andonly one” unless explicitly so stated, but rather “one or more.”Moreover, where a phrase similar to “at least one of A, B, or C” is usedin the claims, it is intended that the phrase be interpreted to meanthat A alone may be present in an embodiment, B alone may be present inan embodiment, C alone may be present in a single embodiment; forexample, A and B, A and C, B and C, or A and B and C. Differentcross-hatching is used throughout the figures to denote different partsbut not necessarily to denote the same or different materials.

Systems, methods and apparatus are provided herein. In the detaileddescription herein, references to “one embodiment”, “an embodiment”, “anexample embodiment”, etc., indicate that the embodiment described mayinclude a particular feature, structure, or characteristic, but everyembodiment may not necessarily include the particular feature,structure, or characteristic. Moreover, such phrases are not necessarilyreferring to the same embodiment. Further, when a particular feature,structure, or characteristic is described in connection with anembodiment, it is submitted that it is within the knowledge of oneskilled in the art to affect such feature, structure, or characteristicin connection with other embodiments whether or not explicitlydescribed. After reading the description, it will be apparent to oneskilled in the relevant art(s) how to implement the disclosure inalternative embodiments.

Furthermore, no element, component, or method step in the presentdisclosure is intended to be dedicated to the public regardless ofwhether the element, component, or method step is explicitly recited inthe claims. No claim element herein is to be construed under theprovisions of 35 U.S.C. 112(f), unless the element is expressly recitedusing the phrase “means for.” As used herein, the terms “comprises”,“comprising”, or any other variation thereof, are intended to cover anon-exclusive inclusion, such that a process, method, article orapparatus that comprises a list of elements does not include only thoseelements but may include other elements not expressly listed or inherentto such process, method or article, or apparatus.

What is claimed is:
 1. A self-emulsifying cannabidiol compositioncomprising from about 1% to about 40% w/w cannabidiol, from about 40% toabout 99% w/w of one or more surfactants selected from polyethyleneglycol 40 hydrogenated castor oil, caprylocaproyl polyoxyl-8 glycerides,linoleoyl polyoxyl-6 glycerides, polyglyceryl-3 dioleate, andpolysorbate 80, and one or more cosolvents selected from propyleneglycol and ethanol, wherein w/w denotes weight by total weight of thecomposition, and wherein said composition forms an emulsion having anaverage globule size from about 30 to about 600 nanometers whendispersed in an aqueous medium.
 2. The composition on of claim 1,further comprising one or more oils selected from glycerylmonolinoleate, glyceryl monooleate, propylene glycol dicaprylocaprate,glycerol monostearate 40-55 and a medium chain triglyceride.
 3. Thecomposition of claim 1, further comprising one or more antioxidantsselected from alpha tocopherol, butylated hydroxy anisole, butylatedhydroxy toluene, ascorbyl palmitate, ascorbic acid, sodium ascorbate,sodium metabisulfite, EDTA, citric acid, sodium bisulfite, sodiumthiosulfate, thioglycerol and propyl gallate.
 4. The composition ofclaim 1, wherein the composition forms an emulsion having an averageglobule size from about 100 to about 300 nanometers when dispersed in anaqueous medium.
 5. The composition of claim 4, wherein the aqueousmedium is gastric fluid.
 6. The composition of claim 1, wherein thecomposition is suitable for delivery to a gastrointestinal tract or amucosa of an oral cavity.
 7. The composition of claim 1, wherein thecomposition is contained in a hard gelatin or soft gelatin capsule.
 8. Aself-emulsifying cannabidiol composition comprising: from about 5% toabout 35% w/w cannabidiol; from about 2% to about 60% w/w polyethyleneglycol 40 hydrogenated castor oil; from about 2% to about 50% w/w of asurfactant selected from caprylocaproyl polyoxyl-8 glycerides, linoleoylpolyoxyl-6 glyceride or a combination thereof; from about 0.1% to about2% w/w alpha tocopherol; from about 5% to about 30% w/w of a cosolventselected from propylene glycol, ethanol and a combination thereof; andfrom about 1% to about 15% w/w polyglyceryl-3 dioleate, wherein w/wdenotes weight by total weight of the composition.
 9. The composition ofclaim 8, wherein the polyethylene glycol 40 hydrogenated castor oil isat a concentration from about 10% to about 50% w/w and the surfactantselected from caprylocaproyl polyoxyl-8 glycerides, linoleoyl polyoxyl-6glyceride or a combination thereof is at a concentration from about 20%to about 40% w/w.
 10. The composition of claim 8, wherein thecomposition forms an emulsion with an average globule size from about100 to about 1,000 nanometers when dispersed in an aqueous medium. 11.The composition of claim 8, wherein the composition forms an emulsion inless than 30 minutes upon contact with an aqueous medium includinggastric fluid.
 12. A self-emulsifying cannabidiol compositioncomprising: about 20.5% w/w cannabidiol; about 12.0% w/w ethanol, about9.0% w/w propylene glycol; about 17.0% w/w polyethylene glycol 40hydrogenated castor oil, about 26.0% w/w caprylocaproyl polyoxy-8glycerides; about 4.0% w/w polyoxyl-6 glycerides; and about 0.4% w/walpha tocopherol, wherein w/w denotes weight by total weight of thecomposition and wherein the composition forms an emulsion with anaverage globule size of about 201 nanometers when dispersed in anaqueous medium.
 13. A method of treating a disease selected fromPrader-Willi syndrome, obesity, graft versus host disease, gelasticseizures/hypothalamic hamartoma neonatal seizures, dystonia, centralpain syndromes, phantom limb pain, multiple sclerosis, traumatic braininjury, radiation therapy, acute graft versus host disease, chronicgraft versus host disease, T-cell autoimmune disorders, colitis, DravetSyndrome, Lennox Gastaut Syndrome, mycolonic seizures, juvenilemycolonic epilepsy, refractory epilepsy, childhood absence epilepsy,schizophrenia, juvenile spasms, West syndrome, infantile spasms,refractory infantile spasms, tuberous sclerosis complex, brain tumors,neuropathic pain, cannabis use disorder, post-traumatic stress disorder,anxiety, early psychosis, Alzheimer's Disease, autism, acne, Parkinson'sdisease, social anxiety disorder, depression, diabetic retinopathy,diabetic nephropathy, diabetic neuropathy, ischemic injury of heart,ischemic injury of brain, chronic pain syndrome, and rheumatoidarthritis comprising administering a composition of claim 1 to a subjectin need thereof.
 14. A method of treating withdrawal symptoms comprisingadministering a composition of claim 1 to a subject in need thereof,wherein the withdrawal symptoms are caused by the subject reducing orquitting use of an opioid, cocaine, heroin, an amphetamine or nicotine.